When Entertainment Weekly its first Power List in November 1990, Lady Gaga (No. 2) was 4 years old and Ben Stiller (No. 11) was doing Eddie Munster impersonations on MTV. Times change, and so does the talent. For our list of the 50 Most Powerful Entertainers, we based our rankings on a mix of criteria. First we looked at the hard numbers (global box office, album sales, TV ratings). We then added in less tangible factors, such as the stars’ influence within their industries, how well their brand translates across platforms, their overall footprint on pop culture, and their general command of the world stage. In other words, we set out to define what true power means in 2010, and to delineate who’s got it, who’s gaining it, and who’s losing it. Here are the results.

1. Johnny Depp AGE 47 CAREER BOX OFFICE* $5.9 billion LAST THREE FILMS* $1.3 billion AVERAGE OPENING WEEKEND** $49.5 million AVERAGE OPENING OF LAST THREE FILMS** $85.4 million

Depp’s career has been a long, strange trip — and ending up the most powerful actor in Hollywood is the weirdest twist of all. He’s rarely followed the standard playbook, choosing roles as misfits (Edward Scissorhands, Gilbert Grape) and oddballs (Ed Wood, Ichabod Crane) over the usual romantic leads and action heroes. With his uncompromising gonzo turn as Capt. Jack Sparrow in Pirates of the Caribbean: The Curse of the Black Pearl in 2003, his stardom went supernova. In the wake of smashes like the Pirates films, Charlie and the Chocolate Factory, and Alice in Wonderland, Depp can do anything he wants. And the one — maybe the only — thing you can be sure of is that he’ll do exactly that. NEXT The Tourist with Angelina Jolie (Dec. 10).

* Global, excluding animated and cameo roles and films recently released ** Domestic, excluding animated and cameo roles and films that opened on fewer than 2,000 screens

2. Lady Gaga AGE 24 U.S. ALBUMS SOLD 5.1 million U.S. DIGITAL TRACKS SOLD 26.4 million YOUTUBE PLAYS 1.1 billion

What did we all talk about before Lady Gaga came along? If the shenanigans of the former Stefani Germanotta seem to own an unhealthy amount of the pop culture conversation these days, it’s because her output has earned it: Since ”Just Dance” hit No. 1 nearly two years ago, she’s had six additional top 10 hits and has almost single-handedly revived the waning art of mainstream music videos. What’s more, she has thrived on the road at a time when many established artists’ tours have been downgraded or canceled altogether. Next Her new album, Born This Way (2011).

Her ratings aren’t what they once were, but Winfrey will leave behind a huge void in daytime when she exits her talk show for good this May. No other chatfest is expected to generate the viewership she did during her peak in syndication: an astonishing 14 million per day. And though starting another (women’s!) cable channel is akin to charging into a minefield, Winfrey makes it look effortless, recruiting the likes of Rosie O’Donnell, Sarah Ferguson, Shania Twain, and Suze Orman to star on shows for OWN: The Oprah Winfrey Network, which launches in January 2011.

Let’s be honest: He remains the biggest star ever to emerge from the American Idol machine, as proven by all the hullabaloo this summer over who would be ”the next Simon” on Fox’s waning musical juggernaut. Apart from exec-producing NBC’s summer sensation America’s Got Talent (and counting his record-label cash thanks to Susan Boyle), Cowell will be AWOL from TV for a full year while he preps a new version of his U.K. megahit The X Factor — which he also owns — to debut on Fox in 2011. No one doubts it’ll be a hit; the only question is, how big?

5. Will Smith AGE 42 CAREER B.O. $5.3 billion LAST THREE FILMS $1.4 billion AVG. OPENING WEEKEND $36.7 million AVG. OPENING LAST THREE FILMS $51.6 million

Sure, Seven Pounds was a rare box office disappointment, but Smith’s status as one of Hollywood’s shiniest global superstars remains untarnished. He’s master of his own destiny and produced four of his last five films. His tenacious work ethic — be it transforming his body for a role (I Am Legend) or promoting his projects across the planet — has studio chiefs swooning. And as for dusting off the ’80s franchise The Karate Kid and turning it into a $354 million star vehicle for his son Jaden? Well, that’s just showing off. NEXT Men in Black III (May 25, 2012).

6. Robert Downey Jr. AGE 45 CAREER B.O. $2.9 billion LAST THREE FILMS $1.2 billion AVG. OPENING WEEKEND $40.5 million AVG. OPENING LAST THREE FILMS $66.7 million

Ten years ago he was getting busted in a hotel room with cocaine and a Wonder Woman costume. Today he’s sober and wearing a new superhero outfit. Iron Man has made Downey one of the great Hollywood comeback stories, and Sherlock Holmes has given him something few A-list actors ever get: two concurrent action franchises. His powers aren’t absolute (his drama The Soloist earned only $38 million worldwide), but even when he’s a white dude playing a white dude playing a black dude (Tropic Thunder), the brother can fly. NEXT Due Date from The Hangover director Todd Phillips (Nov. 5).

7. Sandra Bullock AGE 46 CAREER B.O. $2.7 billion LAST THREE FILMS $666.7 million AVG. OPENING WEEKEND $15.9 million AVG. OPENING LAST THREE FILMS $26.3 million

How does an actress once considered past her prime become Hollywood’s most bankable woman? By starring in two of last year’s biggest hits (The Proposal and The Blind Side), navigating the Oscar circuit with savvy and grace, and handling the implosion of her personal life with remarkable humor. Every movie fan now sympathizes with her, every media outlet covets her, and every studio exec wants to be in business with her. Right now she’s calling all the shots. NEXT Extremely Loud and Incredibly Close with Tom Hanks or Most Wanted with Ryan Reynolds.

She was one of three people Oprah (No. 3) touched base with before announcing that she would be leaving daytime for good. It was a clear sign that TV’s most powerful woman considered DeGeneres to be her heir. Though her year as an American Idol judge wasn’t a crowning achievement, she showed candor and class when explaining her decision to leave. Dr. Oz and soon-to-be host Anderson Cooper may try to muscle in on her turf, but there’s little doubt that DeGeneres will become daytime’s top banana in Winfrey’s wake.